Menopause, HRT and Oral Contraceptives Flashcards
Define menopause?
Permanent cessation of menstruation
Why does menopause occur?
Due to loss of follicular activity
What is the average age range for onset of menopause?
45-55
What does it mean to describe menopause as climacteric?
The patient may go through a transition period
Give 7 symptoms of menopause
- Hot flushes (head, neck, upper chest)
- Urogenital atrophy leading to…
- …Dyspareunia
- Sleep disturbances
- Depression
- Decreased libido
- Joint pain
Outline the normal HPG axis and the changes that occur in relation to it during menopause
- The hypothalamus secretes GnRH
- This stimulates pituitary to secrete LH / FSH
- This stimulates oestrogen and inhibin B from the ovaries
- Oestrogen and inhibin B have negative feeback effects at the pituitary (inhibiting LH / FSH release) and the hypothalamus (inhibiting GnRH)
During menopause:
- The production of oestrogen and inhibin B lowers and thus there is also less negative inhibition on secretion of LH / FSH and GnRH by the pituitary and the hypothalamus respectively
Give 2 possible complications of menopause and explain why this occurs
- Osteoporosis
* Oestrogen is an anabolic hormone which preserves bone structure and so loss of oestrogen could lead to loss of bone matrix and thus osteoporosis - increasing the risk of bone fracture - CVD
- Oestrogen improves the lipid profile and preserves endothelial function
- Therefore loss of oestrogen leads increased risk of CVD
What symptom can HRT help treat in menopause?
Controls vasomotor symptoms - hot flushes
What 2 hormones are given in HRT, and why are they both given? Also, in what case would you only need to give one of these
- Oestrogen
- Progesterone
- Unopposed oestrogen risks the development of endometrial hyperplasia and thus endometrial carcinoma
- Progesterone helps prevent this risk
- IF the patient has had a hysterectomy, they can just have oestrogen becuase there is no risk of endometrial hyperplasia / carcinoma
How can HRT be administered?
- Cyclical - cycling between oestrogen and progesterone - oestrogen every day and progesterone the last 12-14 days
- Continuous combined - both oestrogen and progesterone given, all the time
Give the 4 HRT formulations
- Oral Estradiol (1mg)
- Oral conjugated equine oestrogen (0.625 mg)
- Transdermal oestradiol patch for (50 micrograms
- Intravaginal -relevant for dyspareunia
How well is oestrogen absorbed and what is its bioavailability like?
- Well absorbed
- Low bioavailability due to high first pass metabolism
What are the 2 types of oestrogen provided in HRT (not referring to formulations here), and for one of them describe how it is adapted to have high bioavailability
- Estrone sulphate (oestrogen conjugate)
- Ethinyl oestradiol (semi-synthetic oestrogen) - the ethinyl group protects it from first pass metabolism
Give 5 side effects of HRT
- Breast cancer
- Coronary heart diseaese
- Deep vein thrombosis
- Stroke
- Gallstone
Oestrogen alone has beneficial effects on ….. ….. and ….. ….. but synthetic ….. negate these effects of oestrogen
Oestrogen alone has beneficial effects on lipid profile and endothelial function, but synthetic progestins negate these effects of oestrogen
What risks are there in older people (>60) taking HRT?
- Increased atherosclerosis
- Pro-thrombotic and pro-inflammatory effects of oestrogen
In what age group would you get people getting the beneficial effects of oestrogen and when would you more likely get adverse effects?
- Under 60s you’d get beneficial effects and in over 60s you’d get adverse effects
What is Tibolone, what does it treat, and what risks are it associated with?
- Synthetic prohormone with oestrogenic, progestogenic and weak androgenic actions
- Reduces fracture risk
- Increased risk of stroke (RR: 2.2) and possible increased risk of breast cancer
1) How does Raloxifene work (what’s SERM) and what does it treat?
2) What increased risks is it associated with?
1)
- Selective oestrogen receptor modulator
- Oestrogenic in bone - reduces the risk of vertebral fractures
- Anti-oestrogenic in breast and uterus: reduces breast cancer risk
2)
- Increased risk of VTE
- Increased risk of fatal stroke
1) What is premature oestrogen insufficiency?
2) Causes of premature oestrogen insufficiency?
1)
- Menopause before the age of 40
2)
- Autoimmune
- Iatrogenic - surgery, radiation, therapy
2 drug names for progesterone given as part of HRT
- Levonorgestrel
- Norethisterone
How does HRT in the COCP work to reduce fertility and what 2 substances does it contain?
- Ethinyl oestradiol - causes negative feedback at the hypothalamus/pituitary to reduce fertility
- Levonorgestrel - progestogens thicken cervical mucus - makes implantation harder
1) In what cases would you give progesterone only contraceptives?
2) How are long acting progesterone only therapies administered (what route)?
3) Weaknesses of progesterone only contraceptives?
1)
- When oestrogen use is contra-indicated
2)
- Intra-uterine
3)
- Short half-life
- Short duration of action
2 forms of post-coital contraception and how they work?
1.Copper IUD (intrauterine contraceptive device)
- Affects sperm viability and function
- Contain levonorgestrel (progesterone)
- Ulipristal (can be taken up to 12 hours after intercourse)
- Anti-progestin (progesterone) activity
- Delays ovulation and impairs implantation
What does Tamoxifen do?
- Anti-oestrogenic in breast tissue - treats breast cancer
